Rift Valley fever (RVF) virus (family Bunyaviridae, genus Phlebovirus) is a mosquito-borne pathogen of both livestock and humans found throughout Africa and more recently the Arabian peninsula. Historically, RVF virus has been the cause of either low-level endemic activity or large explosive epizootics/epidemics of severe disease throughout its range (Findlay et al., Lancet ii:1350-1351, 1931; Jouan et al., Res. Virol. 140:175-186, 1989; Ringot et al., Emerg. Infect. Dis. 10:945-947, 2004; Woods et al., Emerg. Infect. Dis. 8:138-144, 2002). RVF outbreaks are characterized by economically disastrous “abortion storms” with newborn animal mortality approaching 100% among livestock, especially sheep and cattle (Coetzer et al., J. Vet. Res. 49:11-17, 1982; Easterday et al., Am. J. Vet. Res. 23:470-479, 1962; Rippy et al., Vet. Pathol. 29:495-502, 1992).
Human infections typically occur either from an infected mosquito bite, percutaneous/aerosol exposure during the slaughter of infected animals, or via contact with aborted fetal materials. Human RVF disease is primarily a self-limiting febrile illness that in a small percentage (about 1-2%) of cases can progress to more serious and potentially lethal complications including hepatitis, delayed onset encephalitis, retinitis, blindness, or a hemorrhagic syndrome with a hospitalized case fatality of 10-20% (Madani et al., Clin. Infect. Dis. 37:1084-1092, 2003; McIntosh et al., S. Afr. Med. J. 58:03-806, 1980). Excessively heavy rainfall in semi-arid regions often precedes large periodic outbreaks of RVF virus activity, allowing for the abundant emergence of transovarially infected Aedes spp. mosquitoes and subsequent initiation of an outbreak by transmission of virus to livestock and humans via infected mosquito feeding (Linthicum et al., Science 285:397-400, 1999; Swanepoel et al., Contributions to Epidemiology and Biostatistics 3:83-91, 1981). The association with abnormally heavy rains provides some ability to predict periods and regions of high disease risk, which in turn provides a potential window of opportunity for targeted vaccination programs if a safe, inexpensive and highly efficacious single dose vaccine were available.
The ability of RVF virus to cross international and geographic boundaries and strain veterinary and public health infrastructures is well documented. In 1977, RVF virus was reported for the first time north of the Sahara desert where an extremely large outbreak affecting more than 200,000 people occurred along the Nile River basin in Egypt (Meegan et al., Contributions to Epidemiology and Biostatistics 3:100-113, 1981). Approximately ten years later in 1987, a large outbreak occurred in western Africa along the border of Mauritania and Senegal affecting an estimated 89,000 individuals (Jouan et al., Res. Virol. 140:175-186, 1989). Later, the virus was isolated for the first time outside of Africa (across the Red sea) in Saudi Arabia and Yemen and was found to be the cause of a large epizootic/epidemic in 2000 with an estimated 2000 human cases and 245 deaths (Anonymous, Morb. Mortal. Wkly. Rep. 49:982-5, 2000; Centers for Disease Control and Prevention, Morb. Mortal. Wkly. Rep. 49:1065-1066, 2000; Shoemaker et al., Emerg. Infect. Dis. 8:1415-1420, 2002).
Most recently, in late 2006 to early 2007, following heavy rainfall in eastern Africa, RVF virus emerged as the cause of a widespread outbreak that eventually resulted in 1062 reported human cases and 315 reported deaths. Associated with the outbreak were substantial economic losses among livestock in southern Somalia, Kenya, and northern Tanzania (Anonymous, Morb. Mortal. Wkly. Rep. 56:73-76, 2007). The ability of RVF virus to cause explosive outbreaks in previously unaffected regions accompanied by high morbidity and mortality during RVF epizootics/epidemics highlights the importance of developing high throughput screening tools for potential antiviral therapeutic agents and the development of safe and efficacious vaccines for this significant veterinary and public health threat.